Cytomegalovirus (CMV) retinitis has become the most common and significant infectious ocular disease associated with the acquired immunodeficiency syndrome (AIDS), affecting approximately 25% of this patient population. While the clinical and histopathologic features of AIDS-associated CMV retinitis have been extensively described, the pathogenic mechanisms involved remain poorly understood. Unfortunately, because of the strict species specificity of human CMV, animal models of human CMV retinitis are not possible. Thus, attempts to develop a clinically relevant animal model of CMV retinitis have focused on related CMVs, such as murine CMV, which has yet to yield a murine model for CMV retinitis. During the past year, we experimentally infected macaques that were seropositive for rhesus CMV with two different simian immunodeficiency virus (SIV) isolates in an attempt to develop a nonhuman primate model of CMV retinitis. From these in vivo studies the following observations were made. 1) Experimental infection of rhesus macaques with SIVmac239 or SIV EvT3 did not result in the reactivation of CMV in the peripheral blood compartment. Studies in HIV-infected patients have shown that human CMV load in the peripheral blood compartment increases prior clinical signs of CMV retinitis. Thus, our studies suggest that SIV infection alone is insufficient at stimulating widespread CMV dissemination. 2) SIV infection was associated with localized CMV disease that caused significant morbidity resulting in the termination of two macaques. Thus, conditions that mediate widespread CMV dissemination need to be determined if this is a prerequisite for CMV retinitis.